University of Tartu researchers made a breakthrough in the development of human papillomavirus drugs

Researchers of the University of Tartu and Icosagen Cell Factory OÜ have published an article in PLOS Pathogens journal, which introduces the new cellular monitoring system for evaluating the growth of human papillomavirus (HPV) and the effect of drugs. The new drug screening system could considerably speed up the development of a new HPV drug. 

“Almost all people get a papillomavirus infection at some point in their life but the majority of infections pass relatively harmlessly, in many people the symptoms never appear,” says Mart Toots, who recently defended his doctoral thesis at the University of Tartu. His dissertation studied the life-threatening or oncogenetic types of the virus.

There are more than 200 subtypes of human papillomaviruses and they may cause illnesses ranging from benign proliferations (for example warts) to throat and cervical cancer. Every year six million people are diagnosed with new HPV infections in the U.S. alone. HPV-caused illnesses are treated using a wide variety of methods with varying success, but no specific cure for HPV infection exists so far.

To aid development of an efficient cure, Mart Toots and his colleagues of Icosagen Cell Factory Ltd. and the University of Tartu have created a new method that enables the identification of potentially effective drugs and drug targets.  Unlike previously developed systems, their method takes into account the full HPV genome, as well as all three stages of the viral life cycle that occur during HPV infection.

To develop the new system, researchers genetically engineered HPV genomes by adding bioluminescent proteins that allow easy monitoring of viral growth at any stage of life cycle.  This enables to quickly test whether a potential drug has an effect on the virus or not, and thereby speed up the development of potential drug candidates.

“We are confident that the developed HPV drug screening assay system will allow to identify several novel drug targets and small-molecule drugs,” the authors explain. “These could be used effectively for the elimination of cutaneous and mucosal low-risk and high-risk infections, thereby addressing serious unmet medical need in society, like benign and malignant HPV-positive epithelial tumours,” the researchers described their goals.

So far, the method has been used to screen more than 1600 chemical compounds, several of which were identified as blocking the growth of some high-risk subtypes of HPV.

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This research was made possible by the collaboration between the Institute of Technology of the University of Tartu, Icosagen AS and Enterprise Estonia.

This research was financed by:

  1. Icosagen Cell Factory OÜ from their own resources.
  2. Icosagen Cell Factory OÜ project EU42266 “Novel platform for development of antiviral drugs against HPV infection” was supported from 2012–2015 by the Enterprise Estonia instrument “Grant for research and development applied research projects” with finances from the European Regional Development Fund.
  3. The University of Tartu Institute of Technology participated in this project as a co-investigator, and used partly resources from the Estonian Research Council (ETAG) grant IUT-20-27, Estonian Science Foundation (ETF) grants 9385 and 9467 and resources of the Centre of Excellence in Chemical Biology (3.2.0101.08-0017).

 

As a result of this research project, five doctoral dissertations were defended in 2016 and three more have been prepared for defence.

Additional information: Mart Ustav, Professor of Biomedical Technology of the University of Tartu, 509 8600, mart.ustav@ut.ee

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